Abstract：
PURPOSE:Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. METHODS:Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations. RESULTS:Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose. CONCLUSION:SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Seto Y,Suzuki G,Leung SS,Chan HK,Onoue Sdoi
10.1007/s11095-016-1887-3subject
Has Abstractpub_date
2016-06-01 00:00:00pages
1447-55issue
6eissn
0724-8741issn
1573-904Xpii
10.1007/s11095-016-1887-3journal_volume
33pub_type
杂志文章abstract：OBJECTIVE:The objective of this work was to determine plasma protein adsorption and macrophage phagocytosis of biodegradable polyanhydride, polylactic acid and polylactic-co-glycolic acid microspheres prepared by both spray-drying and solvent evaporation techniques. METHODS:Microspheres were characterized by scanning ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011935222652
更新日期：1998-02-01 00:00:00
abstract：:The pharmacokinetics of Sb was examined in 29 patients with cutaneous leishmaniasis following the intramuscular administration of a dose of sodium stibogluconate equivalent to 600 mg of Sb. Blood was sampled at different time intervals from each patient and Sb was measured in whole blood by electrothermal atomic absor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016251023427
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:To evaluate the effects of several buffers and excipients on the stability of glucagon during freeze-drying and storage as dried powder formulations. METHODS:The chemical and physical stability of glucagon in freeze-dried solid formulations was evaluated by a variety of techniques including mass spectrometry (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0820-7
更新日期：2012-12-01 00:00:00
abstract：:The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018942127524
更新日期：1994-06-01 00:00:00
abstract：PURPOSE:To dynamically analyze the processes of oral absorption and hepatobiliary distribution of telmisartan using positron emission tomography (PET). METHODS:(11)C-labeled telmisartan ([(11)C]TEL) was orally administered to rats with or without non-radiolabeled telmisartan (0.5, and 10 mg/kg). PET scanning of abdomi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0768-7
更新日期：2012-09-01 00:00:00
abstract：:The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018977021183
更新日期：1992-02-01 00:00:00
abstract：PURPOSE:Scutellarin, a flavonoid derived from the plant Erigeron breviscapus, is currently widely used to treat cerebrovascular diseases, liver-related diseases, and hyperlipidemia in china and other East Asian countries. This study was to investigate the effect of scutellarin on the uptake of rosuvastatin in HEK293T c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02950-5
更新日期：2020-10-29 00:00:00
abstract：:Nucleoside transporters play a critical role in the absorption, disposition, and targeting of therapeutically used nucleosides and nucleoside analogs. This review is focused on the Na(+)-dependent, concentrative nucleoside transporters which are found in a variety of cells including renal, intestinal and hepatic epith...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1012113931332
更新日期：1997-11-01 00:00:00
abstract：PURPOSE:The addition of high amounts of calcium remains a pharmaceutical concern due to its precipitation with phosphate in total parenteral nutrient (TPN) admixtures, compromising also the stability of the lipid emulsion. MATERIALS AND METHODS:Calcium-phosphate solubility was compared when using binary PN solutions v...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9671-7
更新日期：2008-11-01 00:00:00
abstract：:Physiologically-based pharmacokinetic (PBPK) models explicitly incorporate tissue-specific blood flows, partition coefficients, and metabolic processes. Since PBPK models are derived using physiologic parameters and interactions of the compound with tissue components, these models are considered to be "bottom up" as o...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-016-2089-8
更新日期：2017-03-01 00:00:00
abstract：PURPOSE:To study the role of unsaturated fatty acid ester substituents in the autoxidation of polysorbate 80 using quantitative kinetics. METHODS:Oxidation kinetics were monitored at 40 degrees C in aqueous solution by tracking head space oxygen consumption using a fiber optic oxygen sensor with phase shift fluorescen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9946-7
更新日期：2009-10-01 00:00:00
abstract：:A method to provide near-constant sustained release of high molecular weight, water-soluble proteins from polyanhydride microspheres is described. The polyanhydrides used were poly(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their copolymers [P(FAD-SA)]. P(FAD-SA) microspheres containing proteins of differ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018929531410
更新日期：1993-04-01 00:00:00
abstract：PURPOSE:Models to predict membrane-water partition coefficients (Kp) as a function of drug structure, membrane composition, and solution properties would be useful. This study explores the partitioning of dexamethasone (Dex) and its ionizable 21-phosphate (Dex-P) in liposomes varying in acyl chain length, physical stat...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1143-z
更新日期：2013-12-01 00:00:00
abstract：PURPOSE:N-terminal site-specific mono-PEGylation of recombinant human epidermal growth factor (EGF) was accomplished using polyethyleneglycol (PEG) derivatives (Mw = 2000 and 5000) through a reactive terminal aldehyde group. METHODS:The site-specific PEG conjugation was conducted ata slightly acidic pH condition (pH 5...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023402123119
更新日期：2003-05-01 00:00:00
abstract：PURPOSE:We have evaluated a new process, involving solution-enhanced dispersion by supercritical fluids (SEDS), for the production of polymeric microparticles. METHODS:The biodegradable polymers, Poly (DL-lactide-co-glycolide): copolymer composition 50:50 (DL-PLG), Poly (L-lactide) (L-PLA), Poly (DL-lactide) (DL-PLA) ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018868423309
更新日期：1999-05-01 00:00:00
abstract：:The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015822431178
更新日期：1992-03-01 00:00:00
abstract：:Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016380104424
更新日期：1984-05-01 00:00:00
abstract：PURPOSE:The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. METHODS:Crystallization was studied by thermal analysis, microscopy, x-ra...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016223101872
更新日期：1995-10-01 00:00:00
abstract：PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2743-z
更新日期：2020-01-08 00:00:00
abstract：:Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018904825958
更新日期：1993-03-01 00:00:00
abstract：PURPOSE:β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells. METHODS:Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. As HMB is a monocarboxylate, focus was on monoca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2626-3
更新日期：2019-04-17 00:00:00
abstract：PURPOSE:The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. METHODS:Magnetic glyconanoparticl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1021-8
更新日期：2014-06-01 00:00:00
abstract：PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitiz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2484-4
更新日期：2018-09-06 00:00:00
abstract：:Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized by a number of microorganisms. Large-scale fermentation with Aspergillus niger (ATCC 10549) and Nocardia corallina (ATCC 19070) have resulted in the isolation of four microbial metabolites which have been chara...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015845306124
更新日期：1990-02-01 00:00:00
abstract：PURPOSE:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9573-8
更新日期：2008-07-01 00:00:00
abstract：PURPOSE:Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1636-z
更新日期：2015-07-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9009-z
更新日期：2005-01-01 00:00:00
abstract：:The topical antifungal Sch-39304 is a racemic compound comprised of two enantiomers, Sch-42427 and Sch-42426, only one of which (Sch-42427) is pharmacologically active. The pure enantiomers have a lower melting point and, therefore, a higher solubility than the racemic compound. Because of these differences in physico...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018945618264
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its associa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1990-5
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:Covalent binding between N-acetyl-L-cysteine (NAC) and albumin was evaluated kinetically by conducting in vitro experiments. METHOD:After 14C-NAC was incubated with human or rat serum, the solution was analyzed by anion-exchange HPLC. The albumin-bound 14C-NAC was quantified by measuring the radioactivity in t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020749211745
更新日期：2002-11-01 00:00:00
